Lupus is a systemic autoimmune disease resulting in inflammation in multiple organ systems. The disease course is very variable and unpredictable. There is a definite clinical need for better biomarkers for monitoring this disease, particularly renal disease. The current tools available for monitoring lupus and end-organ involvement are not optimal. More reliable tools that detect early disease are warranted. Early detection and prompt treatment can have significant impact on morbidity and disease course. There is also a need for better biomarkers that can be used to assess treatment response in clinical trials. Our completed studies using a couple of targeted proteomic platforms have uncovered several serum or urine proteins that are elevated in lupus patients with elevated SLE disease activity index. From our completed studies, and newly proposed targeted proteomic screens, we will assemble a panel of about 40 serum or urine biomarkers. We will ascertain if these novel biomarkers have the potential to identify lupus patients with active renal disease, monitor disease activity serially, predict treatment response or project long-term outcome in these patients. Besides their biomarker potential, the protein markers examined in this proposal may also constitute therapeutic targets as they exhibit a variety of interesting functional attributes. Better non-invasive biomarkers can significantly improve disease management in patients with lupus nephritis.